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Brown adipose tissue (BAT) is the major site of sympathetically activated adaptive thermogenesis during cold exposure and after spontaneous hyperphagia, thereby controlling whole-body energy expenditure and body fat. Recent radionuclide studies have demonstrated the existence of metabolically active BAT in healthy adult humans. Human BAT is activated by acute cold exposure, being positively correlated to cold-induced increases in energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, either repeated cold exposure or daily ingestion of some food ingredients acting on transient receptor potential channels recruited BAT in association with increased energy expenditure and decreased body fat even in individuals with low BAT activities before the treatment. Thus, BAT is a promising therapeutic target for combating human obesity and related metabolic disorders.

Brown adipose tissue (BAT) burns fat to produce heat when the body is exposed to cold and plays a role in energy metabolism. Using fluorodeoxyglucose-positron emission tomography and computed tomography, we previously reported that BAT decreases with age and thereby accelerates age-related accumulation of body fat in humans. Thus, the recruitment of BAT may be effective for body fat reduction. In this study, we examined the effects of repeated stimulation by cold and capsinoids (nonpungent capsaicin analogs) in healthy human subjects with low BAT activity. Acute cold exposure at 19°C for 2 hours increased energy expenditure (EE). Cold-induced increments of EE (CIT) strongly correlated with BAT activity independently of age and fat-free mass. Daily 2-hour cold exposure at 17°C for 6 weeks resulted in a parallel increase in BAT activity and CIT and a concomitant decrease in body fat mass. Changes in BAT activity and body fat mass were negatively correlated. Similarly, daily ingestion of capsinoids for 6 weeks increased CIT. These results demonstrate that human BAT can be recruited even in individuals with decreased BAT activity, thereby contributing to body fat reduction.

Capsaicin and its nonpungent analog (capsinoids) are known to be food ingredients that increase energy expenditure and decrease body fat. This article reviews the role of brown adipose tissue (BAT) for the thermogenic effect of these compounds in humans and proposes the possibility of some other antiobesity food ingredients.A single oral ingestion of capsinoids increases energy expenditure in human individuals with metabolically active BAT, but not those without it, indicating that capsinoids activate BAT and thereby increase energy expenditure. This finding gave a rational explanation for discrepant results of the effects of capsinoids in the previous studies. Human BAT may be largely composed of inducible 'beige' adipocytes more than typical brown adipocytes because its gene expression patterns are similar to beige cells isolated from murine white fat depots. In fact, preadipocytes isolated from supraclavicular fat deposits - where BAT is often detected - are capable of differentiating into brown-like adipocytes in vitro, providing evidence of inducible brown adipogenesis in adult humans.As human BAT may be inducible, a prolonged ingestion of capsinoids would recruit active BAT and thereby increase energy expenditure and decrease body fat. In addition to capsinoids, there are numerous food ingredients that are expected to activate BAT and so be useful for the prevention of obesity in daily life.

Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented diet-induced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitol's effect on brown adipose tissue could lead to a novel anti-obesity drug.

This paper analyzes the capacity choice issue under a price-setting mixed duopoly with differentiated goods, when the objective function of the private firm is its relative profit. In this paper, we show that the public firm chooses over-capacity irrespective of the degree of product differentiation and the degree of importance of the relative performance of the private firm. In contrast, we find that the difference between the output and capacity levels of the private firm strictly depends on both the degree of product differentiation and the degree of importance of its relative performance. More precisely, the private firm chooses over-capacity when the degree of importance of its relative performance is high relative to the degree of product differentiation, whereas it chooses under-capacity otherwise.

This paper studies capacity choice in a quantity-setting mixed duopoly with differentiated goods, when the objective function of the private firm is its relative profit. In this paper, we show that the differences between the output levels and capacity levels between both the public firm and the private firm strictly depend on both the degrees of product differentiation and of importance of the private firm’s relative performance. More precisely, we find that the public firm chooses over-capacity when both the degrees of importance of the private firm’s relative performance and of product differentiation are sufficiently high whereas it chooses under-capacity otherwise, and further the private firm chooses under-capacity when the degree of importance of its relative performance is high as compared the degree of product differentiation whereas it chooses over-capacity otherwise.

Purpose Brown adipose tissue (BAT) contributes to the regulation of non-shivering thermogenesis and adiposity. Increasing BAT has recently attracted much attention as a countermeasure to obesity. Animal studies have shown that prolonged catechin treatment increases uncoupling protein 1, a thermogenic protein in BAT. On the other hand, supportable evidence in human is lacking. Thus, the purpose of this study was to examine whether BAT increases after catechin ingestion in humans. Methods Twenty-two healthy young women were given either a catechin-rich (540 mg/day; catechin) or placebo beverage every day for 12 weeks in a double-blind design. BAT density was measured using near-infrared time-resolved spectroscopy (NIRTRS), visceral fat area were measured using magnetic resonance imaging, extramyocellular lipids (EMCL) using proton magnetic resonance spectroscopy, and body fat mass using dual-energy X-ray absorptiometry scans. Results BAT density was significantly increased (18.8 %), and EMCL was decreased (17.4 %) after the 12-week ingestion. There was a significant negative correlation between the changes in BAT density and those in EMCL (r = −0.66, P

Brown adipose tissue (BAT) contributes to whole body energy expenditure (EE), especially cold-induced thermogenesis (CIT), in humans. Although it is known that EE and CIT vary seasonally, their relationship with BAT has not been investigated. In the present study, we examined the impact of BAT on seasonal variations of EE/CIT and thermal responses to cold exposure in a randomized crossover design. Forty-five healthy male volunteers participated, and their BAT was assessed by positron emission tomography and computed tomography. CIT, the difference of EE at 27°C and after 2-h cold exposure at 19°C, significantly increased in winter compared with summer, being greater in subjects with metabolically active BAT (High BAT, 185.6 kcal/day vs. 18.3 kcal/day, P < 0.001) than those without (Low BAT, 90.6 kcal/day vs. −46.5 kcal/day, P < 0.05). Multivariate regression analysis revealed a significant interaction effect between season and BAT on CIT ( P < 0.001). The cold-induced drop of tympanic temperature (Tty) and skin temperature (Tskin) in the forehead region and in the supraclavicular region close to BAT deposits were smaller in the High BAT Group than in the Low BAT Group in winter but not in summer. In contrast, the drop of Tskin in the subclavicular and peripheral regions distant from BAT was similar in the two groups in both seasons. In conclusion, CIT increased from summer to winter in a BAT-dependent manner, paralleling cold-induced changes in Tty/Tskin, indicating a role of BAT in seasonal changes in the thermogenic and thermal responses to cold exposure in humans.

Human brown adipose tissue (BAT) activity (SUVmax) has been typically evaluated by 18F-fluorodeoxy glucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT). In this study, the objective was to detect human BAT by near-infrared time-resolved spectroscopy (NIRTRS), a noninvasive and simple method for measuring total hemoglobin concentration [total-Hb] and reduced scattering coefficient (μs') in the tissue. The [total-Hb] in the supraclavicular region of the BAT (+) (SUVmax≥2.0) group was 95.0±28.2 μM (mean+/-SD), which was significantly higher than that of the BAT (-) (SUVmax2.0) group (52.0±14.8 μM), but not in other regions apart from the BAT deposits. The μs' in the supraclavicular region of the BAT (+) group was 8.4±1.7 cm(-1), which was significantly higher than that of BAT (-) group (4.3±1.0 cm(-1)), but not in other regions. The area under the receiver operating characteristic curve closest to (0, 1) for [total-Hb] and μs' to discriminate BAT (+) from BAT (-) was 72.5 μM and 6.3 cm(-1), respectively. The sensitivity, specificity, and accuracy for both parameters were 87.5, 100, and 93.3%, respectively. Our novel NIRTRS method is noninvasive, simple, and inexpensive compared with FDG-PET/CT, and is reliable for detecting human BAT.

Ruthenium (Ru) thin films were grown on thermally-grown SiO2 substrates by plasma enhanced atomic layer deposition (PEALD) using a sequential supply of a new betadiketonate Ru metallorganic precursor, dicarbonyl-bis(5-methyl-2,4-hexanediketonato) Ru(II) (C16H22O6Ru) with a high vapor pressure and NH3 plasma as a reactant at the substrate temperature ranging from 175 and 310 degrees C. A self-limited film growth was confirmed at the deposition temperature of 225 degrees C and the growth rate was 0.063 nm/cycle on the SiO2 substrate with very short number of incubation cycles (approximately 10 cycles). The resistivity of PEALD-Ru films was dependent on the microstructural features characterized by grain size and crystallinity, which could be controlled by varying the deposition temperature. Ru film with the resistivity of -20 μΩ-cm and high density of 11.5 g/cm3 was obtained at the deposition temperature as low as 225 degrees C. It formed polycrystalline structure with hexagonal-close-packed phase that was confirmed by X-ray diffractometry and transmission electronic microscopy analysis. Step coverage of PEALD-Ru film deposited with the optimum condition was good (-75%) at the very small-sized trench (aspect ratio: -4.5 and the top opening size of 25 nm).

Human brown adipose tissue (BAT) activity (SUVmax) has been typically evaluated by 18F-fluorodeoxy glucose (FDG)–positron emission tomography (PET) combined with computed tomography (CT). In this study, the objective was to detect human BAT by near-infrared time-resolved spectroscopy (NIRTRS), a noninvasive and simple method for measuring total hemoglobin concentration [total-Hb] and reduced scattering coefficient (μs′) in the tissue. The [total-Hb] in the supraclavicular region of the BAT (+) (SUVmax ≥ 2.0) group was 95.0 ± 28.2 μM (mean +/− SD), which was significantly higher than that of the BAT (−) (SUVmax < 2.0) group (52.0 ± 14.8 μM), but not in other regions apart from the BAT deposits. The μs′ in the supraclavicular region of the BAT (+) group was 8.4 ± 1.7 cm−1, which was significantly higher than that of BAT (−) group (4.3 ± 1.0 cm−1), but not in other regions. The area under the receiver operating characteristic curve closest to (0, 1) for [total-Hb] and μs′ to discriminate BAT (+) from BAT (−) was 72.5 μM and 6.3 cm−1, respectively. The sensitivity, specificity, and accuracy for both parameters were 87.5, 100, and 93.3 %, respectively. Our novel NIRTRS method is noninvasive, simple, and inexpensive compared with FDG-PET/CT, and is reliable for detecting human BAT.

Proinsulin C-peptide shows beneficial effects on microvascular complications of Type 1 diabetes. However, the possible occurrence of membrane C-peptide receptor(s) has not been elucidated. The aim of this study was to identify and characterize membrane proteins to which C-peptide binds. The enzyme α-enolase was co-immunoprecipitated with C-peptide after chemical cross-linking to HL-60 cell surface proteins and identified by mass spectrometry. Recombinant α-enolase activity was modulated by C-peptide, with a significant decrease in K(m) for 2-phosphoglycerate without affecting V(max). The enzyme modulation by C-peptide was abolished when C-terminal basic lysine residue (K434) of the enzyme was replaced by neutral alanine or acidic glutamate, but not with basic arginine. The enzyme modulation by C-peptide was reproduced with the C-peptide fragments containing glutamate corresponding to position 27 (E27) of the full-length C-peptide. Addition of a lysine analogue to the assay and A31 cell culture abrogated the enzyme modulation and MAP kinase activation by C-peptide, respectively. The results indicate that C-peptide has the capacity to activate α-enolase through a specific interaction between E27 of the peptide and K434 of the enzyme. Since α-enolase plays a role as a cell surface receptor for plasminogen, it may conceivably also serve as a receptor for C-peptide in vivo.

Background: Capsinoids—nonpungent capsaicin analogs—are known to activate brown adipose tissue (BAT) thermogenesis and whole-body energy expenditure (EE) in small rodents. BAT activity can be assessed by [ 18 F]fluorodeoxyglucose–positron emission tomography (FDG-PET) in humans. Objectives: The aims of the current study were to examine the acute effects of capsinoid ingestion on EE and to analyze its relation to BAT activity in humans. Design: Eighteen healthy men aged 20–32 y underwent FDG-PET after 2 h of cold exposure (19C) while wearing light clothing. Whole-body EE and skin temperature, after oral ingestion of capsinoids (9 mg), were measured for 2 h under warm conditions (27C) in a single-blind, randomized, placebo-controlled, crossover design. Results: When exposed to cold, 10 subjects showed marked FDG uptake into adipose tissue of the supraclavicular and paraspinal regions (BAT-positive group), whereas the remaining 8 subjects (BAT-negative group) showed no detectable uptake. Under warm conditions (27C), the mean (6SEM) resting EE was 6114 6 226 kJ/d in the BAT-positive group and 6307 6 156 kJ/d in the BATnegative group (NS). EE increased by 15.2 6 2.6 kJ/h in 1 h in the BAT-positive group and by 1.7 6 3.8 kJ/h in the BAT-negative group after oral ingestion of capsinoids (P , 0.01). Placebo ingestion produced no significant change in either group. Neither capsinoids nor placebo changed the skin temperature in various regions, including regions close to BAT deposits. Conclusion: Capsinoid ingestion increases EE through the activation of BAT in humans. This trial was registered at clinicaltrial.gov as UMIN 000006073. Am J Clin Nutr doi: 10.3945/ajcn.111.018606.

健康づくりの目的は、健康増進のみならず生活の質(Qualify of life: QOL)の向上にある。メタボリックシンドローム (metabolic syndrome: MetS)は生活習慣と密接に関連しており、健康習慣の変容によって改善が可能である一方、病態が進行すると日常生活活動の制限につながりQOL は低下する。本研究では、食行動変容によるMetS の病態改善がQOL の変化にどのように影響しているかを示す構造を明らかにすることを目的とした。「天使健康・栄養クリニック」を受講した平均年齢60.8 歳の87 名(男性35 名、女性52 名)を対象に、トランスセオレティカルモデル(Transtheoretical Model: TTM)に基づいて、3ヶ月間教育的に指導・支援を行った。その結果、食行動変容段階得点やその他の健康関連指標値が高まり、食物エネルギー摂取量が低下し、MetS 診断指標値が改善するとともにQOL 得点が上昇した。QOL の向上には、指導・支援後の食行動社会的支援 (食行動social support: 食行動SS) 得点、腹囲変化率、拡張期血圧変化率が回帰された。さらに、QOL の向上には、食行動SS を介した食行動変容段階の向上によって改善した健康習慣指数(Health practice index: HPI)や腹囲の変化が関連している構造モデルが得られた。MetS の改善がQOL の向上に関連するとともにその向上に至る構造が明らかになった。, The purpose of health promotion is not only to enhance health but also to improve the quality of life (QOL). Metabolic syndrome (MetS) can be alleviated through a change in health habits as it is closely linked to lifestyle. However, when left untreated, MetS will limit the daily activities of the affected individual and reduce his/her QOL. This study aims to analyze the structural equation modeling of relationships between QOL, eating behavior change, and MetS. We recruited 87 individuals (35 males, 52 females; mean age 60.8 years) who attended a program conducted by Tenshi Health and Nutrition Clinic. The participants received educational intervention for 3 months; the intervention was based on the transtheoretical model of behavior change. The intervention resulted in improved QOL scores, along with an improvement in the stage of eating behavior change, increased health-related indicator levels, decreased dietary energy intake, and improved MetS index level. After intervention, improvement in QOL was correlated with the scores of social support (SS) for eating behavior change (eating behavior SS) as well as with the changing rates of abdominal circumference and diastolic blood pressure. These results indicated a structural equation modeling that QOL improvement was related to changes in health practice index and abdominal circumference. Both changes resulted from improvement in the stage of eating behavior facilitated by improved eating behavior SS. Further research is required to elucidate the structural modeling involved in the enhancement of QOL associated with the alleviation of MetS.

「天使健康栄養クリニック」は、地域住民を対象にメタボリックシンドロームの予防・改善を目的として開催されている。本クリニックでは、講話並びに個人面談によって健康教育と変容支援を行っている。2008 年度および2009 年度に本クリニックに参加し修了した人たちを対象として、4ヶ月間における運動行動、ストレス対処・休養行動および食行動の変容について、個別に検討した。クリニック全8回のうち1、3、5、7回目に計4回、対象者に実施した質問紙調査から行動変容ステージ(得点)を評価した結果、3種の健康行動は、平均的には第1回目に比べて4回目には行動変容ステージ(得点)が高まり変容がみられた。しかし、個々人でみると第1回目から4回目までの変容は直線的ではない対象者も多かった。第1回目に比べて4回目に変容ステージ(得点)が高まった対象者の他に変化しなかった者、低下した者も見られたので、そのような違いの要因を面談記録から推察した。運動行動変容に関する事例検討から、上昇・改善者では、歩行を中心に運動が継続されていたが、継続しようという強い意欲と支援がうまく関連していたと考えられる。, The Tenshi Health and Nutrition Clinic is a health awareness and guidance course offered to local residents for the prevention and alleviation of metabolic syndrome. The clinic, which is run over eight non-consecutive days, comprises lectures and personal interviews, and aims to help participants improve health awareness and progress through the stages of behavioral change. In this study, changes in exercise behavior, stress management and resting behavior, and dietary behavior were individually assessed over a four-monthe period in participants who completed the clinic in 2008 and 2009. Scores indicative of the stage of behavioral change (behavioral change scores) were obtained from questionnaires completed by participants on days one, three, five, and seven of the clinic. On an average, the behavioral change scores for all three types of health-improving behavior were higher in the fourth questionnaire survey than in the first one, suggesting that the participants had progressed through the stages of behavioral change. However, the results of the four questionnaire surveys showed that the time-dependent changes in health-improving behavior are not linear for many participants. When the behavioral change scores of the fourth survey were compared with those of the first survey, they were higher in some participants, but lower or unchanged in others. Information obtained from individual interviews indicated that continuous effort was made to maintain an exercise routine, in particular walking, by participants who made progress in changing their behaviors. The results suggest that with regard to participants who improved their exercise behavior, the support provided was positively linked with the strong will to continue an exercise routine.

地域住民を対象にメタボリックシンドローム(MetS)予防を目的とした健康教室「天使健康栄養クリニック」(以下、クリニック)を開催している。本研究では、参加者個々人の運動行動の変容段階に着目し、変容段階に合わせた運動実施の支援による体力向上とMetS予防・改善の関連について明らかにすることを目的として、教室終了時に運動行動変容段階を実行期以上に高めた者と高めなかった者とで比較検討を行なった。対象は、クリニックを受講し修了した58名(男性22 名、女性36 名)であり、運動行動変容段階、自己効力感(SE)や、ソーシャルサポート(SS)、体力、身体組成、血液検査値、栄養摂取量等を測定した。その結果、運動行動変容段階を実行期以上に高めた参加者は、実行期まで至らなかった参加者に比べて、SE 得点やSS得点が高まり、体力指標が向上し、腹囲や生化学検査値、血圧などMetS診断指標値の改善度合いが高かった。クリニックでは、運動実施以外に食事と休養の行動変容を指導・支援しているため、食事内容が改善するなど生活全般が健康的に変容したが、運動を日常的に継続して実行できるようになることで、体力が向上すると同時に、MetS 診断指標値の改善が進むことが示唆された。, The Tenshi Health and Nutrition Clinic is a health awareness and guidance course offered to local residents for the prevention and alleviation of metabolic syndrome. In this study, we focused on the stages of exercise behavior changes in individual participants to reveal the association of improvement in physical fitness, achieved by stage-matched exercise guidance, with prevention and alleviation of metabolic syndrome. Participants (n=58; 22 men, 36 women) were divided into two groups according to whether they had reached the action stage in the behavior change model by the end of the clinic(A-group or B-group). The stage of change in exercise behavior, self efficacy (SE) and social support (SS) scores, physical fitness, body composition, blood test results, and nutrient intake were compared between the groups. SE and SS scores and physical fitness indices were higher in participants who reached at least the action stage (A-group) than in those who had not (B-group). In addition, improvements in the values of diagnostic indices of metabolic syndrome, such as abdominal circumference, biochemical test results, and blood pressure, were more prominent in A-group than in B-group. The clinic offered consultation and guidance on diet and resting, as well as on exercise. Thus, overall lifestyle including eating habits improved among the participants. This study shows that adopting a daily and continuous exercise behavior enhances physical fitness and improves the values of diagnostic indices in metabolic syndrome.

ヒマワリは近年，バイオマスエネルギーを得るための油糧作物として注目されており，今後栽培面積の増加が予想される．しかし，栽培において大きな問題となるのが鳥害であると考えられる．つくば市の中央農業総合研究センターのヒマワリ圃場4ヶ所，計100aにおいて，キジバトStreptopelia orientalis，カワラヒワCarduelis sinica，スズメPasser montanusがヒマワリを採食しているのを確認した．27回の調査で延べ飛来個体数はそれぞれ，70羽，5,277羽，318羽，調査日あたりの出現頻度はそれぞれ，44.4％，100％，37.0％で，延べ飛来個体数，出現頻度ともカワラヒワが最も多く，最大300羽の群れで採食していた．ヒマワリの食害は花弁がまだ残っている時期から収穫時まで続き，食害を調査した2つの圃場（50aと30a）において，食害されたヒマワリの割合はそれぞれ30.8％と72.1％となり，播種日が早かった圃場で食害が大きかった．ヒマワリを栽培する際には鳥害対策を行わないと収量の大幅な低下につながる可能性が示唆された．

Brown adipose tissue (BAT) is a site of sympathetically activated adaptive nonshivering thermogenesis, thereby being involved in the regulation of energy balance and body fatness. Recent radionuclide imaging studies have revealed the existence of metabolically active BAT in adult humans. Human BAT is activated by acute cold exposure and contributes to cold-induced increase in whole-body energy expenditure. The metabolic activity of BAT is lower in older and obese individuals. The inverse relationship between the BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. In fact, repeated cold exposure recruits BAT in association with increased energy expenditure and decreased body fatness. The stimulatory effects of cold are mediated through the activation of transient receptor potential (TRP) channels, most of which are also chemesthetic receptors for various naturally occurring substances including herbal plants and food ingredients. Capsaicin and its analog capsinoids, representative agonists of TRPV1, mimic the effects of cold to decrease body fatness through the activation and recruitment of BAT. The well-known antiobesity effect of green tea catechins is also attributable to the activation of the sympathetic nerve and BAT system. Thus, BAT is a promising target for combating obesity and related metabolic disorders in humans.

In this paper we analyze the capacity choice in a mixed duopoly, considering the separation between ownership and management of firms. We introduce the following two alternatives as each firm's delegation type to its manager: (i) partial delegation—delegating only the quantity setting, and (ii) full delegation—delegating the determination of both capacity and quantity levels. First, we investigate each firm's capacity scale relative to its quantity, given its delegation type. Second, we derive the equilibrium delegation type of each firm under the endogenous decision by its owner. Finally, we consider the effect of privatization on each firm's delegation type and social welfare.

Leptin is an adipocyte-derived peptide hormone that acts on the brain and regulates food intake and energy balance. Several previous reports have suggested that overwintering raccoon dogs Nyctereutes procyonoides are able to control their adiposity efficiently, but the contribution of leptin to weight regulation in these animals remains unclear. To study the seasonality of overwintering raccoon dogs as well as the effects of fasting on them, serum leptin levels were investigated using a newly established canine leptin-specific enzyme-linked immunosorbent assay (ELISA) kit. Of the nine animals studied, five were fed and four were fasted (deprived of food for 2 months in winter). Blood samples and body fat weights were monitored once a month throughout the experimental period (July 2007–March 2008). Leptin concentrations obtained by ELISA were significantly higher than and had a positive correlation with those obtained by previously used multispecies radioimmunoassay (RIA) kits. Moreover, ELISA showed a clearer correlation between the body fat weight and leptin levels compared with RIA, suggesting the efficacy of canine leptin-specific ELISA kit for leptin estimation in raccoon dogs. Autumnal fattening was observed in both groups of animals, but the wintertime loss of adipose tissue was more obvious in the fasted group. Serum leptin concentrations determined by ELISA showed seasonal changes without significant differences between the fed and fasted animals. Therefore, high levels of leptin may be responsible for the suppression of feeding behavior in raccoon dogs before winter. J. Exp. Zool. 315:84–89, 2011. © 2010 Wiley-Liss, Inc.

メタボリックシンドローム(メタボ)予防を目指した「天使健康栄養クリニック」を2006年と2007年に開設し、地域住民58名を対象に食事や運動、健康行動への介入支援指導を約3ヶ月間に渡って行い、腹囲や血圧、血中成分などのメタボ関連指標の変化を調べた。介入前後での平均値を比較すると、男女間で若干の違いがあるものの、腹囲と血糖が有意に低下し、血圧と中性脂肪も低下傾向が認められた。メタボの診断基準からメタボおよび予備群の判定を行い、人数を比較したところ、3ヶ月の介入によってメタボ該当者は10名から9名に、予備群は31名から28名に、それぞれ減少したことがわかった。これらの結果から、本クリニックはメタボの予防・改善に一定の効果があると結論した。なお、介入の効果には大きな個人差が見られたので、今後はこれらを考慮した介入方法の検討が必要であろう。, Tenshi Health and Nutrition Clinic aimed to identify methods for preventing metabolic syndrome by conducting studies for 3 months in 2006 and 2007. A total of 58 participants underwent medical examinations, including measurement of waist circumference, blood pressure, and blood biochemistry, before and after a 3 month support program. This program consisted of lectures and counseling for improving dietary and physical activities. The program decreased the waist circumference and blood glucose, blood pressure, and blood triglyceride levels of the participants to a certain extent, thereby leading to a slight decrease in the number of patients diagnosed with metabolic syndrome. Thus, Tenshi Health and Nutrition Clinic have developed a program for the prevention of metabolic syndrome, although further modifications of this program may be necessary.

インスリン抵抗性の上流に位置する内臓脂肪型肥満は、メタボリックシンドロームの必須条件であり、BMI による量的肥満とは区別される。減量に伴う肥満指標と血中因子との関連を検討し、肥満指標を規定する食事因子を明らかにすることを目的にした。天使健康栄養クリニックを受講した平均年齢59.1歳の58名(男性22、女性36)を対象に、3ヶ月間の栄養と運動指導を行った。開始時及び3 ヶ月指導後に身体計測、血圧測定、採血と血液生化学検査、連続3日間の撮影法による食事調査を行った。3ヶ月で体重は男性で3.5%、女性で3.3%減少し、体脂肪率も減少した。腹囲は男性93.5 cm から90.1、女性92.6 cm から89.7と減少した。摂取エネルギーは男性34.5kcal/kg/day から29.9, 女性33.0から29.1と減少した。血中中性脂肪とHOMA 指数の変化には腹囲が回帰されたが、体重との関連は認めなかった。腹囲減少率には、体重とは独立して食事脂質量が回帰され、エネルギー補正後も同様であった。メタボリックシンドロ-ムのKey Factor である腹囲には、食事由来のエネルギー摂取量とは独立して脂質摂取総量の寄与が大きい可能性が示唆され、今後の検討に繋がる知見であった。, Visceral fat accumulation, upstream of insulin resistance, is the characteristic condition of metabolic syndrome; this feature distinguishes metabolic syndrome from obesity assessed using body mass index. In the present study, we aimed to evaluate weight loss associated correlations between obesity indices and factors in blood to identify the dietary factors that regulate the obesity indices. Dietary and exercise guidance was provided for 3 months to 58 participants (22 male, 36 female;mean age, 59.1 years) who attended a program at Tenshi Health and Nutrition Clinic to prevent and/or improve metabolic syndrome. Measurement of body size and blood pressure, blood collection and biochemical analysis, and a 3 day (consecutive) dietary survey were performed before and after the participants received guidance. After the program, the weights of the male and female participants had decreased by 3.5% and 3.3% , respectively, and the body fat percentage of the participants had also decreased. The average abdominal circumference of the male participants was reduced from 93.5 cm to 90.1 cm, and that of female participants reduced from 92.6 cm to 89.7 cm. The average amount of energy consumed by the male participants reduced from 34.5 to 29.9 kcal/kg・day-1 and that of the female participants was also reduced from 32.9 to 28.9 kcal/kg・day-1. The amount of calories consumed at lunch, dinner, and snack time decreased in the male group, while those consumed at dinner and snack time decreased in the female group. Consumption of sugar was reduced while that of fruit was increased in the male group: while consumption of grain and fat was reduced in the female group. Changes in triglyceride concentration in blood and the HOMA index scores correlated with the changing rate of abdominal circumference, but did not correlate with the weight changing rate. The reduction rate of abdominal circumference was independent of weight, but was correlated with the reduction in the amount of fat present in meals. This rate remained unchanged after energy intake correction. These findings suggest that abdominal circumference, which is believed to be a key factor of metabolic syndrome, is influenced by the total amount of fat contained in meals, but is independent of caloric intake, this possibility must be further studied in further studies.

Roll casting of Al-25mass%Si hyper eutectic aluminum alloy strip was tried by an unequal diameter twin roll caster. The casting speed was 10m/min. The thickness of the strip was about 2mm. The eutectic Si and primary crystallized Si were very fine by the effect of the rapid solidification. The size of the primary crystallized Si was not uniform at the thickness direction. The primary crystallized Si at the near surface was finer than that of inside. The eutectic Si was finer than 2μm. The strip could be cold rolled after hot rolling and annealing.

Di-uracil substituted cyclen derivatives were prepared by the reaction of cyclen with 6-chloro-1-methyluracil or 6-chloro-1,3-dimethyluracil. The reaction of cyclam with 6-chloro-1,3-dimethyluracil gave a similar di-uracil substituted cyclam. The 1,7-di-uracil substituted cyclen was converted to the tricyclic guanidinium salt and acylurea upon heating in DMSO in the presence of weak acid. The 1,8-di-uracil substituted cyclam gave a tricyclic dihydroimidazolium salt under the same conditions. These reactions can be explained by an intramolecular uracil ring-breaking reaction mechanism.

This is the first paper to consider the endogenous timing in mixed duopoly with subsidization. Pal (Economics Letters, Vol. 61 (1998), pp. 181–185) shows that private leadership is always an equilibrium outcome in a mixed duopoly without any subsidy. By including the production subsidy, we observe that private leadership may disappear from equilibrium and that Cournot and public leadership become the likely equilibrium outcomes. Furthermore, we find that when firms have identical technologies the first-best allocation can be attained by the same subsidy before and after privatization even though firms' production timings are endogenized. Finally, we examine privatization with lobbying activities and show that such privatization leads to the deterioration of social welfare.

Subcutaneous adipocytes accumulate excess energy as triglycerides, but lipolytic response is less sensitive to catecholamines than visceral adipocytes. Obesity also induces catecholamine resistance of adipocytes. We have searched for crude drugs that could enhance the lipolytic response to noradrenalin. In this study, the lipolysis-promoting activities and action mechanisms of a novel plant extract from Hemerocallis fulva (HE) were investigated in isolated adipocytes from rat subcutaneous fat. HE exhibited no lipolysis-promoting activity alone but markedly promoted lipolysis when combined with noradrenaline; however, this synergistic activity was accompanied by no increase of intracellular cAMP production. This activity of HE was also observed when combined with cAMP analogue and was further enhanced by phosphodiesterase inhibitor. PKA inhibitor could reduce these activities of HE. These results indicate that HE is a novel lipolysis-promoting material that can sensitize the lipolytic response of adipocytes to catecholamine and suggest that HE can amplify the intra-cellular signaling pathway related to PKA or modify the other mechanism-regulating lipase activity. This characteristic material could contribute to improvement of adipose mobility in obesity-related disorder or in subcutaneous adiposity and to suppression of body fat accumulation.

Among Tissue kallikrein genes (KLKs), KLK1 is abundantly expressed in human skin. Although its putative promoter is known to have various cis-elements, they have not been functionally tested. In the present study, the regulation mechanism of KLK1 promoter supporting such abundant expression was examined. Luciferase assay targeting the KLK1 promoter (nucleotide − 1153/+ 40 from the major transcriptional start site) was performed on NHEK human keratinocyte. − 954/− 855, − 428/− 236, and − 100/+ 40 had the induction activity. The motif search program failed to find unique binding motifs in − 428/− 236, whereas both − 954/− 855 and − 100/+ 40 had a unique GATAs binding motif. Electrophoretic mobility shift assay (EMSA) and DNA footprinting confirmed the binding of NHEK nuclear protein to these motifs that were supershifted by anti-GATA3 antibody. Among GATA isoforms, GATA3 alone could be amplified in RNA obtained from NHEK. Moreover, introduction of GATA3 into fibroblastic NIH3T3 cells enhanced the activity of KLK1 promoter containing − 954/+ 40, while that of GATA3 dominant negative mutant to NHEK cells impaired the same promoter's activity. Thus, GATA3 was found to bind the site located at − 954/− 855 and to be a key regulator of abundant KLK1 expression in human keratinocyte.

This paper studies capacity choice in a mixed duopoly with differentiated goods under quantity competition and price competition, taking into account the separation between ownership and management. In this paper, we show that in equilibrium, under quantity competition, both the public firm and the private firm choose over capacity, while under price competition, both choose under capacity. Moreover, in both the competition types, we found that the results do not depend on the degree of product differentiation. Furthermore, under both the competition types, we conduct detailed analysis of each firm`s delegation parameter of managerial contract, and we compare the equilibrium market outcomes obtained in our model with those in the entrepreneurial case, which is considered in several existing literature, and those in the private duopolistic case, which corresponds to the one after privatization of the public firm.

Bioelectrical impedance analysis (BIA) is widely used for assessing the total body, and sometimes visceral, fat content. However the reliability of the results remains to be confirmed, especially for their relationship to the blood parameters associated with obesity and metabolic syndrome. We analyzed the relationship between some blood parameters and the body fat content evaluated by standard X-ray computed tomography (CT) and BIA. Fifty-eight male and 52 female healthy subjects (20-72 years old with a body mass index of 16.3-30.6 kg/m2) underwent both CT and BIA. The visceral fat content was consistently higher in the males than females, regardless of the method used. However, the absolute value by BIA was higher than that by CT. The total and visceral fat contents of the females assessed by CT were positively correlated with the blood leptin, glucose, HbA1c and triglyceride levels, and negatively with adiponectin. The total and visceral fat contents of the males were also positively correlated with the leptin, HbA1c, triglyceride, and insulin levels, and negatively with adiponectin and HDL cholesterol. Similar correlations were also found for the males when the fat contents were assessed by BIA. However, apparently different relationships were found for the females when assessed by BIA compared with those by CT. Assessing body fat by BIA may give some results different from those estimated by the standard CT method, particularly for the relationship with obesity-associated blood parameters.

Present paper is an analytical study on a patch repair problem. An exact solution based on a simplified plate model is obtained for single-patch-repaired circular plates with axisymmetric debondings between the patch and the base plate subjected to a uniform radial displacement, where significant bending deformation occurs owing to asymmetric configuration of the repaired plate. The debondings locate both at the outside edge of the patch and at the edge of the hole. The theoretical solution agreed well with a finite element solution. The basic mechanism of debonding problem of two dimensional patch repaired plate is discussed through the present theoretical solution and the finite element solutions. The nonlinear finite element results show that nonlinear effect is significant, while the nonlinear solution finally approaches the linear solution obtained by neglecting bending deformation. The linear solutions of energy release rate of the debonding crack with and without considering bending effect gives an upper and a lower limit. The linear exact solution neglecting bending deformation is applicable as a rough estimate at an early design stage since not only the solution gives upper limit but also the effect of the bending deformation on energy release rate of debonding crack decays quickly with the increase of the applied inplane displacement.

Proton-coupled monocarboxylate transporters (MCTs) are essential for the transport of lactate, ketone bodies, and other monocarboxylates through the plasma membrane. The present immunohistochemical study aimed to examine the expression of MCTs in the brown adipose tissue (BAT) of mice. An intense immunoreactivity for MCT1 was found in the plasma membrane of brown adipose cells at light and electron microscopic levels but not in white adipose cells. The expression of MCT1 in BAT was confirmed by Western blot and in situ hybridization analyses. In fetuses (E17.5) and neonates, the MCT1 mRNA expression of BAT was abundant and appeared more intense than that in adult animals. These results, together with the intense expression of CD147 (a functional partner of MCTs) and acetyl-CoA carboxylase-2 (a component of fatty acid oxidation) in perinatal periods, suggest the involvement of MCT1 in the uptake of monocarboxylates from the circulation for thermogenesis rather than lipogenesis.

Adiponectin is an adipokine that is specifically expressed in adipose tissues, directly sensitizes the body to insulin via specific receptors and its decreased plasma concentration is responsible for insulin resistance in obese humans. Diabetes is an important problem also in veterinary medicine, and feline diabetes is very similar to human type 2 diabetes, in which obesity is an important risk factor. In the present study, We obtained cDNA clones corresponding to feline adiponectin and adiponectin receptor 1 (AD-R1), whose nucleotide and deduced amino acid sequences were highly identical to those of other species, especially, the extra-cellular domain of feline AD-R1 was almost identical to that of human AD-R1. Adiponectin mRNA was exclusively detected in the adipose tissue, but AD-R1 was in all tissues tested in this study. Next, plasma samples were collected from 22 cats visiting veterinary practices. They were divided to 2 groups based on a five-point scale body condition score (BCS), such as normal group (BCS ranged from 2.5 through 3.5) and obese group (BCS ranged from 4.0 through 5.0). Plasma adiponectin in obese cats (7.2 +/- 1.5 microg/ml) was significantly lower than that of normal cats (18.0 +/- 3.2 microg/ml). These results suggest that adiponectin may be responsible for insulin function also in the cat, and it can be a target molecule for treatment of obesity and diabetes in cats.

ヒヨドリHypsipetes amaurotisの営巣密度を推定するために，茨城県南部において南北36 km，東西18 kmの地域を調査範囲とし，ヒヨドリのさえずり場所を調査した．なお，ヒヨドリは明確にさえずりと区別できる音声を持たないが，繁殖期の早朝，梢など見晴らしのよいところで，大きく高い音声を長く出しており，そのような音声をこの論文中ではさえずりとし，その地点をさえずり地点とした．調査範囲内に設定した32の1 km四方の調査グリッドにおいて，540のさえずり地点を確認した．ポアソン回帰分析を用いてヒヨドリの生息密度に及ぼす環境要因を調べると「森林」，「畑地・草地」，「市街地」が選択され，「水田」は選択されなかった．構築されたモデルよりヒヨドリのさえずり個体数は，調査範囲で12,317個体，密度は19個体/km2と推定された．ヒヨドリは一夫一妻で主にオスのみがさえずることから，これらを2倍した繁殖個体数は24,634個体，密度は38個体/km2と推定された．土地利用割合に基づくクラスター分析により調査範囲を5つに類型化すると，ヒヨドリの推定営巣密度が最も高くなったのは，(1) 森林が優占するクラスターのグリッド（65.4個体／km2）であった．以下ヒヨドリの推定生息密度が低くなる順に，(2) 市街地が優占するグリッド，(3) 畑地・草地が優占するグリッド，(4) 水田が優占するグリッド，(5) 水域が優占するグリッドとなった．対象地内の市街地や畑地・草地にも樹木が見られることから，ヒヨドリの営巣場所選択においては，樹林地の面積割合と樹木の存在が重要であることが示唆された．

Present paper is an analytical work on a patch repair problem. An exact solution is obtained for double lap patch-repaired circular plates with debondings between the two patches and the base plate subjected to a uniform axisymmetric radial displacement, where no bending deformation is considered. The explicit solution based on a simplified plate model excellently agreed with a finite element solution. Through a parametrical study on the strain distribution and the energy release rates for the debondings based on the analytical solution, various general rules on the design of the patch repairs are elaborated.

Purpose: Acute respiratory distress syndrome is characterized by neutrophil accumulation in the lungs and the activation of several cytokines produced by macrophages. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects and inhibits the activation of macrophages, in addition to its inotropic and vasodilatory effects. The purpose of this study was to examine the beneficial effects of olprinone on lipopolysaccharide (LPS)-induced pulmonary inflammation. Materials and methods: Lung inflammation was produced by intravenous LPS injection into rats. The rats were divided into four groups: a vehicle group in which normal saline was injected, an olprinone group in which olprinone was injected at a dose of 0.2 mg/kg, a dexamethasone group in which dexamethasone was injected at a dose of 5 mg/kg, and a control group. In each group, drug was injected intraperitoneally 30 min before the intravenous administration of LPS. The blood was obtained at 1 h and then animals were sacrificed at 6 h and blood and lung specimen were obtained for cytokine analysis and pathological examination. On another set of experiment, bronchioloalveolar lavage (BAL) was performed for cytokine analysis of BAL fluid. The macrophages isolated from normal rat by BAL were cultured in vitro with the presence of LPS and olprinone or dexamethasone, and supernatant was collected. The levels of several cytokines in the serum, in the BAL fluid, and in the culture supernatant were determined. Results: The animals injected with LPS were found to have an influx of neutrophils in the lungs, and inflammatory cytokines, such as TNF-α and IL-6, and anti-inflammatory cytokine IL-10 were produced. Pretreatment with olprinone or dexamethasone significantly inhibited the LPS-induced neutrophil influx into the lungs, suppressed inflammatory cytokines TNF-α and IL-6. The level of anti-inflammatory cytokine IL-10 increased in an olprinone group. The inhibition of TNF-α and IL-6, and the augmentation of IL-10 release were also observed in in vitro culture of isolated rat alveolar macrophages when olprinone (10−5 mol/ml) and LPS (10 μg/ml) were cultured together. However, the level of IL-10 in serum and culture supernatant was suppressed in a dexamesathone group. Conclusion: LPS-induced lung inflammation is strongly inhibited by olprinone accompanying the enhancement of IL-10 and the inhibition of inflammatory cytokines. Results of the in vitro experiment suggest that alveolar macrophages may play an important role in ameliorating LPS-induced lung inflammation and the mechanism of its effect is different from that of steroid.

Background Proinsulin C-peptide shows ameliorative effects on diabetic complications, possibly through the production of nitric oxide (NO). On the contrary, increased local availability of NO and expression of endothelial NO synthase (eNOS) in the renal endothelium are shown to be involved in the progression of diabetic nephropathy. The aim of this study was to elucidate the effect of C-peptide and insulin as a reference on the eNOS expression in the early phase of type 1 diabetic rat kidney. Methods Type 1 diabetes in rats was produced by streptozotocin injection and some of the rats were treated with either C-peptide or insulin by the aid of an osmotic pump for 1 week. Conventional biochemical and histological analyses were performed on tissue samples. Results The diabetic rats showed hyperglycemia with over 90% reduction of endogenous insulin and C-peptide. Replacement with C-peptide or insulin resulted in recovery of weight lost, but only insulin infusion lowered plasma-glucose concentration. The eNOS protein was localized in glomeruli and endothelial cells of arterioles, and its amounts in the kidneys, but not in the lungs, of diabetic rats was increased. Replacement with C-peptide or insulin-abrogated diabetes-induced increase of renal eNOS protein. Conclusion The results indicate that C-peptide suppresses diabetes-induced abnormal renal eNOS expression, by which C-peptide may exert beneficial effects on diabetic nephropathy. Copyright © 2007 John Wiley & Sons, Ltd.

勿来工場で製造されるノーカーボン紙は，当初，衝撃による品質不良を保護するため，手包装によるダンボールケース詰で出荷されていた。ノーカーボン紙の生産量が増加するに伴い，手包装では間に合わなくなったため，巻取り包装機を使用したストレッチフィルム包装に切り替えた。しかし，最近の環境保護意識の高まりから，ユーザーではフィルムごみの処理問題が深刻化した。そこで，勿来工場では新しく環境にやさしい包装荷材を開発した。新荷材の特長はフィルムレス，再生可能，防湿，耐衝撃性などの性能が挙げられる。さらに，この荷材を用いて，ノーカーボン紙分野では他社に類を見ないフィルムレス包装の自動ラベル貼り付け装置，自動パレット積み装置などを持つ完全自動巻取り包装機を稼動させた。本報ではノーカーボン紙の斬新な包装仕様と巻取り自動包装機の操業経験について報告する。

Summary Leptin is proposed to reduce body fat by increasing energy expenditure, in addition to decreasing food intake, through the activation of brown adipose tissue (BAT) thermogenesis. To confirm this, we investigated the effects of leptin on whole body energy expenditure, BAT functions and adiposity in wild-type (WT) mice, and compared with those in mice deficient in uncoupling protein 1 (UCP1), a key molecule for BAT thermogenesis. Chronic hyperleptinemia induced by adenovirus gene transfer reduced food intake in both WT and UCP1-KO mice. WT mice with hyperleptinemia, compared to pair-fed controls, showed increased oxygen consumption, elevated UCP1 expression in BAT, ectopic UCP1 induction in white adipose tissue (WAT), and reduced body fat content. These effects of chronic hyperleptinemia were not observed in UCP1-KO mice. It was concluded that the fat-reducing effect of leptin is due to not only decreased food intake, but also increased UCP1-dependent energy expenditure.

Leptin is an adipose tissue-derived cytokine plays key roles in the regulation of food intake and energy expenditure. However, regulatory mechanisms of leptin gene expression are not fully elucidated in ruminants that utilize short-chain fatty acids (SCFA), known as volatile fatty acids, as principal energy sources. In this study, we determined effects of SCFA and long-chain fatty acids (LCFA) on leptin expression in bovine adipocytes. Bovine stromal vascular cells isolated from subcutaneous adipose tissue of Holstein cows were cultured to confluence and treated sequentially with dexamethasone and isobutylmethylxanthine for 2 days and insulin and troglitazone for 12 days to achieve full differentiation to adipocytes. The cells started to accumulate lipids 4 days after the onset of treatment, with increased mRNA expression of leptin, as well as aP2, adiponectin, and PPAR-gamma. Removal of fetal calf serum and reduction of glucose in the culture medium of differentiated adipocytes decreased leptin mRNA expression. Subsequent addition of acetate, butyrate, or propionate dose-dependently restored and rather increased leptin expression, while addition of LCFA suppressed it. The stimulatory effect of acetate was abolished by prior treatment of the cells with pertussis toxin and by addition of LCFA. Furthermore, cows fasted for 48h and fed thereafter, elaborate reduced and increased plasma leptin levels, respectively. Thus, these results suggest that plasma leptin levels in cows are inversely controlled at the transcription level by VFA and LCFA, and that the effects of SCFA possibly act through a G protein-coupled receptor for SCFA.

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARgamma and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARgamma, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARgamma, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARgamma expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARgamma mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

A selective beta3-adrenoceptor agonist, AJ-9677, was reported to ameliorate obesity and insulin resistance in KK-Ay mice. We examined the acute and chronic effects of AJ-9677 on obese dogs. Oral administration of AJ-9677 (0.01 or 0.1 mg/kg) to overnight fasted obese beagles produced a dose-dependent rise in the plasma levels of non-esterified fatty acids and insulin in 1h, followed by a gradual drop of the plasma glucose level. It produced no apparent abnormal behaviors, but easily detectable cutaneous flushing. Daily treatment of AJ-9677 at a lower dose (0.01 mg/kg) for three weeks produced no notable change in body weight, but at a higher dose (0.1 mg/kg) it reduced the body weight compared to a placebo treatment after seven weeks. Computed tomographic examinations revealed a remarkable reduction of body fat after the AJ treatment, being consistent with the histological observations that the adipose tissue of AJ-9677-treated dogs consisted of smaller and some multilocular adipocytes. The plasma levels of leptin and adiponectin were decreased and increased, respectively, after the AJ treatment, reflecting the reduction of adiposity. It was concluded that AJ-9677 is useful for the treatment of obesity in the dog.

The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1β/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1β using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1β injection (5 μg/kg ip) increased body temperature (+1.82°C at 20 min), decreased physical activity (−37% at 1 h), and produced a slight and insignificant rise (+15% at 1 h) in oxygen consumption (V̇o2). V̇o2 dependent on metabolic thermogenesis (ΔV̇o2 thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1β injection (726 ± 200 ml·h−1·kg−1 at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 ± 87 ml·h−1·kg−1 of ΔV̇o2 thermogenesis at 1 h. In contrast, CL316,243, a selective activator of BAT thermogenesis, increased body temperature, decreased physical activity, and produced a significant rise in V̇o2 in WT mice, showing 1,229 ± 35 ml·h−1·kg−1 of ΔV̇o2 thermogenesis at 1 h. These changes were not observed in UCP1-deficient mice. These results, conflicting with a previously proposed idea of a role of BAT in fever, suggest a minor contribution of BAT thermogenesis to IL-1β-induced fever. In support of this, we found no effect of IL-1β on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.

Leptin is a cytokine produced by adipocytes, and plays a key role in the regulation of energy balance. In the present study, we measured plasma leptin concentrations of 166 normal and obese dogs visiting veterinary practices, and clarified the influence of age, gender and breed on plasma leptin levels in dogs. Leptin levels were higher in the dogs with higher body condition scores. There was no noticeable influence of age, gender and breed, but those in optimal puppies and obese Miniature Dachshund tended to be lower than those in corresponding groups. We conclude that plasma leptin is a reliable marker of adiposity in dogs regardless of age, gender and breed variations, and thereby useful as a blood biochemistry test for health examinations and treatment of obesity.

Uncoupling protein 1 (UCP1) is present exclusively in brown adipose tissue, and contributes to body temperature control during cold exposure. We cloned UCP1 cDNA of plateau pika (Ochotona dauurica), a small, non-hibernating, diurnal lagomorph that inhabits in relatively cold climates and at high altitudes in Mongolia and in northern China. The nucleotide sequence of pika UCP1 was highly homologous to UCP1 of other species, and the deduced amino acid sequence had some common domains for UCP, including six mitochondrial carrier protein motifs and a putative purine-nucleotide binding site. RT-PCR and Western blot analyses revealed that both UCP1 mRNA and protein were expressed exclusively in the interscapular adipose tissue. These results suggest that pika UCP1 contributes to heat production in brown adipose tissue, as do those in other species.